Patients with advanced oesogastric adenocarcinoma that have received at least one previous chemotherapy line with platinium salt and fluoropyrimidin and with a documented progression. MedDRA version: 23.1 Level: LLT Classification code 10084873 Term: Gastrooesophageal junction cancer metastatic System Organ Class: 100000004864
Conditions
Interventions
Product Name: spartalizumab
Product Code: PDR001
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: SPARTALIZUMAB
Current Sponsor code: PDR001
Concentration unit: mg milli
Sponsors
ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically or cytologically documented locally advanced or metastatic oesogastric adenocarcinoma. - Unresectable tumor. - Patients must have received at least one prior systemic chemotherapy based on platinium salt and fluoropyrimidine with documented progression during chemotherapy. - Patients must have received trastuzumab in case of HER2 positive tumor (HER2 +++ or HER2++ and FISH or SISH+) - Determination of tumor MET amplification by FISH available - ECOG Performance Status = 1. - Measurable tumoral disease according to RECIST 1.1 criteria. - Patients must be willing and able to swallow and retain oral medication. - Age =18 years. - Women of childbearing potential and males who are sexually active must agree to follow instructions for method(s) of contraception for the duration of study treatments with Capmatinib and Spartalizumab until 7 days after the last dose of Capmatinib and 150 days after the last dose of Spartalizumab - Consent to participate in the trial after information - Affiliated to a social security system Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: - Previous treatment with immunotherapy or MET inhibitor - Impossibility to take oral medication - Presence or history of another malignant disease that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include: completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type. - Use of any live vaccines within 4 weeks of initiation of study treatment. - History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs). - History or current interstitial lung disease or non-infectious pneumonitis - Active autoimmune disease or a documented history of autoimmune disease (Patients with vitiligo, controlled type I diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted). - Allogenic bone marrow or solid organ transplant - uncontrolled active infection - Human Immunodeficiency Virus (HIV) infection - Untreated active Hepatitis B infection (HBsAg positive) (Patients with active hepatitis B (HBsAg positive) may be enrolled provided viral load (HBV DNA) at screening is 480 ms in women and 470 ms in men), family history of idiopathic sudden death or congenital long QT syndrome. - Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) = 160 mm Hg and/or Diastolic Blood Pressure (DBP) = 100 mm Hg, with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening. - Pregnancy or breastfeeding or women of child-bearing potential, unless they are using highly effective methods of contraception. - Sexually active males unless they use a condom during intercourse while taking capmatinib and for 7 days after stopping treatment and should not father a child in this period. - Participants receiving treatment with strong inducers of CYP3A and could not be discontinued = 1 week prior to the start of treatment. - Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date of first dose of study treatment. - Patient having out of range laboratory values defined as: - Total bilirubin >2 mg/dL, except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN or direct bilirubin >1.5 x ULN - Alanine aminotransferase (ALT) >5 x ULN - Aspartate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the tumor response to the regimen at 6 months after inclusion;Secondary Objective: To evaluate the safety of the regimen during the first and second cycles of administration (up to day 42 (D42)) (cf chap 4.1.2.) - To evaluate the safety and tolerability of the regimen during the whole course of treatment for all kind of toxicities and up to 2 years for immunotherapy-related toxicity (cf chap 10.3.2.) - To characterize the tumor response to the regimen (duration, time to response) - To estimate the progression free survival, up to 2 years after inclusion - To estimate the overall survival, up to 2 years after inclusion - According to the results of interim analysis: to evaluate tolerance and efficacy of spartalizumab monotherapy in patient with non-amplified MET tumor ;Primary end point(s): Overall response rate (ORR) defined as the proportion of patients with at least one objective tumor response (complete or partial) according RECIST v1.1 criteria, within 6 months (8 treatment cycles) after inclusion. Response will be evaluated by thoraco-abdomino-pelvic CT-scan (or abdominal MRI and thoracic CT-scan without injection if contraindication) CT-scan every 9 weeks, with independent centralized reading;Timepoint(s) of evaluation of this end point: within 6 months (8 treatment cycles) after inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Unacceptable toxicity within the first and second treatment cycle (occurrence of the event between D1 to D42 included), defined using the NCI-CTCAE v 4.0 criteria, as follows: - Adverse event which is considered a toxicity > grade 3 at least possibly related to the study treatment. AND - Adverse event > grade 3 which is unrelated to disease, disease progression, intercurrent illness, or concomitant medications AND - Any of the following events: - Any non-hematological toxicity = grade 3 (except for nausea, vomiting, fatigue) - Recurring grade 2 pneumonitis - Myocarditis grade =2 - Autoimmune hemolytic anemia, hemolytic uremic syndrome, or acquired hemophilia grade =3 - Guillain-Barre, severe peripheral or autonomic neuropathy, or transverse myelitis - Encephalitis or aseptic meningitis - Laboratory abnormality = grade 3 lasting >7 consecutive days (except for Nephritis (Grade 3 and 4: Creatinine >3x ULN), for combined elevations of AST or ALT and Total Bilirubin (see details in section 7.1.2 «Criteria for dose reduction / interruption») and for hyperglycaemia and changes in serum electrolytes/enzymes without clinical impact) - Hematological toxicities defined as: Febrile neutropenia (absolute neutrophil count [ANC] 7 consecutive days, grade 4 neutropenia, grade 4 thrombocytopenia or bleeding requiring a platelet transfusion - Adverse event requiring permanent treatment discontinuation more than 21 days - Any other study drug related toxicity considered significant enough to be qualified as unacceptable toxicity in the opinion of the investigators after discussion with the sponsor. Unacceptable toxicity during the whole treatment course (occurrence of the event between D1 to treatment discontinuation), defined using the NCI-CTCAE v 4.0 criteria as above (see below). All adverse events during the whole treatment course, graded according to the NCI-CTCAE v 4.0 criteria before each | — |
Countries
France
Contacts
Public ContactDRCI
ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS
Outcome results
None listed